PUBLICATION

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Authors
Giannaccini, M., Usai, A., Chiellini, F., Guadagni, V., Andreazzoli, M., Ori, M., Pasqualetti, M., Dente, L., Raffa, V.
ID
ZDB-PUB-171104-3
Date
2017
Source
Cellular and molecular life sciences : CMLS   75(7): 1255-1267 (Journal)
Registered Authors
Andreazzoli, Massimiliano
Keywords
Glaucoma, Magnetic nanoparticles, Neurotrophins, Ocular drug delivery, Zebrafish
MeSH Terms
  • Animals
  • Brain-Derived Neurotrophic Factor/administration & dosage
  • Brain-Derived Neurotrophic Factor/chemistry
  • Brain-Derived Neurotrophic Factor/pharmacology
  • Drug Delivery Systems
  • Glaucoma/metabolism
  • Glaucoma/pathology
  • Humans
  • Nanoparticles/chemistry*
  • Nerve Growth Factor/administration & dosage
  • Nerve Growth Factor/chemistry
  • Nerve Growth Factor/pharmacology
  • Nerve Growth Factors/administration & dosage
  • Nerve Growth Factors/chemistry
  • Nerve Growth Factors/pharmacology*
  • Neuroprotection/drug effects*
  • Oxidative Stress/drug effects*
  • PC12 Cells
  • Rats
  • Retina/drug effects*
  • Retina/metabolism
  • Retinal Ganglion Cells/drug effects
  • Retinal Ganglion Cells/metabolism
  • Tumor Cells, Cultured
PubMed
29098325 Full text @ Cell. Mol. Life Sci.
Abstract
Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.
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